Magnesium has been reported as an effective medical therapy in an expanding array of conditions. Evidence investigating magnesium's use is presented, with a number of studies suggesting it should be seriously considered in such conditions as ischemic heart disease, cardiac arrhythmias, and asthma. Magnesium balance and metabolism are briefly reviewed, and then various hypotheses are presented that may explain magnesium's physiologic mechanisms of action, most likely involving calcium and potassium flux across cellular membranes in smooth muscle. In a number of the conditions to be discussed, it has been uncertain whether magnesium administration serves the purpose of merely correcting an underlying deficiency state or of utilizing a specific pharmacologic effect of magnesium. Magnesium deficiency is a relatively common condition, and predisposing factors as well as recent methods for assessing total body stores of magnesium are discussed. Physicians should be familiar with the numerous conditions and therapeutics that are risk factors for an underlying magnesium deficiency and in which empiric magnesium replacement should be considered. Guidelines for administration of parenteral magnesium are presented with specific focus on the low risk of adverse effects, as suggested by the large and rapid dosing regimens used in many of the clinical studies discussed here.